Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of
Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism
of its anti-cancer activity on hormonal independent prostate cancer remains elusive.
Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on
Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination
of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC
staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species
(ROS) and cell cycle analysis.
Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and
showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential,
reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further
confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results.
Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment
of androgen-independent prostate cancer.